Probing for genes in seronegative spondyloarthropathy

Seronegative spondyloarthropathies are a group of disorders characterized by inflammation of the spine, sacroiliac joints, and peripheral arthritis along with various characteristic extra-articular features. Their pathogenesis and immunogenetics have not yet been fully elucidated. Ankylosing Spondylitis (AS) is probably the best studied of these disease. It has now been 27 years since the association of human leukocyte antigen (HLA) B27 and AS has been demonstrated. Since then, a plethora of association studies and linkage studies unequivocally demonstrate that genetic determinants within or near the major histocompatible complex (MHC) are critical to the etiology of AS. Surprisingly though, the total MHC contribution to AS has been estimated at only 30%. In this review, we highlight the genetic basis of AS as the prototypical chronic axial arthritis, and discuss the rationale and approach in searching for non-HLA linked genes.